Abstract

Oestrogens are critical mediators of multiple and diverse physiologic effects throughout the body in both sexes, including reproductive, cardiovascular, endocrine, nervous, and immune systems. Alterations in oestrogen function play important roles in many diseases and pathophysiological conditions. Oestrogens mediate their effects through multiple cellular receptors, the nuclear receptor family (ERα and ERβ) and the G protein–coupled receptor (GPCR) family (GPR30/G protein–coupled oestrogen receptor [GPER]). Although both receptor families can initiate rapid cell signalling and transcriptional regulation, the nuclear receptors are traditionally associated with regulating gene expression, whereas GPCRs are recognized as mediating rapid cellular signalling. The protective and beneficial effects of oestrogen mimicked by selective GPER agonism which were absent or reduced in GPER knockout mice, suggest an essential and a parallel role for GPER in the actions of oestrogen. G protein-coupled oestrogen receptor (GPER) has important transcription dependent outcomes in the regulation of cell growth and programmed cell death secondary to GPER-regulated second-messenger pathways. GPER is expressed ubiquitously and has diverse biological effects such as regulation of endocrine, immune, neuronal and cardiovascular functions. The most important consequences of GPER activation are the regulation of cell growth, migration and apoptotic cell death. These cell growth regulatory effects are important in cancer biology and in the regulation of cardiac and vascular hypertrophy and the response to ischemia, for which GPER is emerging as a novel therapeutic target and prognostic indicator.